Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

In recent years， with the increasing understanding of the genetic mechanisms of hypertrophic cardiomyopathy， novel molecular-targeted drugs Mavacamten and Aficamten are two cardiac myosin inhibitors currently approved by the FDA for the treatment of hypertrophic obstructive cardiomyopathy. Both of them have a similar mechanism of action and can selectively bind to different variable sites of cardiac myosin to inhibit cardiac myosin， thus reducing myocardial hypercontractility. Relevant clinical studies have also shown that both drugs can reduce patients’ left ventricular outflow tract pressure gradient， the levels of N-terminal pro-B-type natriuretic peptide and cardiac troponin I as cardiac markers， and improve New York Heart Association （NYHA） cardiac function class. They are safe， have mild adverse reactions， and can be tolerated by patients. Compared to Mavacamten， Aficamten， as a structurally optimized product， has a shorter half-life and fewer drug-drug interactions， which is more conducive to drug- targeted dose titration.

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO₂ nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8⁺ and CD4⁺ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Purpose: Knowing the distinction between benign and borderline/malignant phyllodes tumors (PTs) can help in the surgical treatment course. Herein, we investigated the value of magnetic resonance imaging-based texture analysis (MRI-TA) in differentiating between benign and borderline/malignant PTs. Methods: Forty-three women with 44 histologically proven PTs underwent breast MRI before surgery and were classified into benign (n = 26) and borderline/malignant groups (n = 18 [15 borderline, 3 malignant]). Clinical and routine MRI parameters (CRMP) and MRI-TA were used to distinguish benign from borderline/malignant PT. In total, 298 texture parameters were extracted from fat-suppression (FS) T2-weighted, FS unenhanced T1-weighted, and FS first-enhanced T1-weighted sequences. To evaluate the diagnostic performance, receiver operating characteristic curve analysis was performed for the K-nearest neighbor classifier trained with significantly different parameters of CRMP, MRI sequence-based TA, and the combination strategy. Results: Compared with benign PTs, borderline/malignant ones presented a higher local recurrence (p = 0.045); larger size (p < 0.001); different time-intensity curve pattern (p = 0.010); and higher frequency of strong lobulation (p = 0.024), septation enhancement (p = 0.048), cystic component (p = 0.023), and irregular cystic wall (p = 0.045). TA of FS T2-weighted images (0.86) showed a significantly higher area under the curve (AUC) than that of FS unenhanced T1-weighted (0.65, p = 0.010) or first-enhanced phase (0.72, p = 0.049) images. The texture parameters of FS T2-weighted sequences tended to have a higher AUC than CRMP (0.79, p = 0.404). Additionally, the combination strategy exhibited a similar AUC (0.89, p = 0.622) in comparison with the texture parameters of FS T2-weighted sequences. Conclusion MRI-TA demonstrated good predictive performance for breast PT pathological grading and could provide surgical planning guidance. Clinical data and routine MRI features were also valuable for grading PTs.

Objective:To investigate the effect of positive and negative pressure extubation on mechanical ventilation patients in the intensive care unit (ICU).Methods:A prospective randomized controlled study was performed, 105 ICU patients who successfully passed the spontaneous breathing test (SBT) after mechanical ventilation of Nanjing Jiangbei Hospital Affiliated to Nantong University from January 2019 to March 2021 were enrolled. According to random number table method, they were randomly divided into positive pressure extubation group (53 cases) and negative pressure extubation group (52 cases). During extubation, all patients were placed in semi-decubitus position (raising the head of bed at an angle range from 30°- 45°), the secretions from mouth, nose, throat and trachea were removed. In the negative pressure extubation group, the sputum suction tube was inserted into the tracheal tube and passed over the distal opening to carry out continuous negative pressure suction in the tracheal tube after disconnecting the ventilator. Meanwhile, after the tracheal tube balloon was evacuated, the sputum suction tube was pulled out together with the tracheal tube. In the positive pressure extubation group, the patients were guided to inspiratory forcibly under the original SBT mode. When the patients reached the inspiratory peak, the ballon was evacuated and the tracheal tube was removed. After extubation, all patients were given nasal catheter oxygen inhalation (oxygen flow 5 L/min). Arterial blood gas analysis indexes [pH value, arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2)] were recorded 5 minutes and 1 hour after extubation in both groups. Vital signs (including tachypnea, tachycardia, elevated blood pressure and decreased oxygen saturation) and complications (including severe cough, airway hyperresponsiveness and pneumonia) were observed 30 minutes after extubation in both groups. Results:Five minutes after extubation, blood gas analysis showed that the PaO 2 of positive pressure extubation group was significantly higher than that of negative pressure extubation group [mmHg (1 mmHg≈0.133 kPa): 123.4±30.2 vs. 111.0±21.1, P < 0.05], the pH value and PaCO 2 in positive pressure extubation group were slightly lower than that of negative pressure extubation group [pH value: 7.411±0.042 vs. 7.419±0.040, PaCO 2 (mmHg): 39.7±4.7 vs. 40.5±5.6], but the differences were not statistically significant (both P > 0.05). One hour after extubation, the pH value, PaO 2 and PaCO 2 in positive pressure extubation group were slightly lower than those in negative pressure extubation group, but the differences were not statistically significant. Within 30 minutes after extubation, the incedences of tachypnea, tachycardia, elevated blood pressure and oxygen desaturationin in positive pressure extubation group were significantly lower than those in negative pressure extubation group [tachypnea: 9.4% (5/53) vs. 28.8% (15/52), tachycardia: 15.1% (8/53) vs. 32.7% (17/52), elevated blood pressure: 11.3% (6/53) vs. 30.8% (16/52), oxygen desaturation: 7.5% (4/53) vs. 34.6% (18/52), all P < 0.05], the incidence of severe cough in positive pressure extubation group was significantly lower than that in negative pressure extubation group [9.4% (5/53) vs. 30.8% (16/52), P < 0.05], but there was no significant difference in the incidence of complications of airway hyperresponsiveness between the two groups [1.9% (1/53) vs. 5.8% (3/52), P > 0.05]. No pneumonia occurred in both groups within 48 hours after extubation. Conclusion:The positive pressure extubation method can ensure full oxygenation of patients undergoing mechanical ventilation in ICU, avoid hypoxia, and reduce the occurrence of hypoxia and severe cough, which is more conducive to the stability of vital signs.

Objective:To investigate the diagnostic value of neutrophil CD64 index in sepsis patients in intensive care unit (ICU).Methods:A prospective case-control study was conducted, the patients admitted to ICU of Jiangbei People's Hospital Affiliated to Nantong University from December 2016 to June 2020 were enrolled. According to the criteria of Sepsis 3, 107 patients diagnosed with sepsis were classified as the sepsis group, 112 patients without infection were classified as control group. Peripheral venous blood samples were collected within 24 hours after ICU admission, neutrophil CD64 index, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC) were detected. Receiver operating characteristic curve (ROC curve) was used to evaluate the diagnostic value of neutrophil CD64 index, CRP, PCT and WBC for sepsis.Results:The neutrophil CD64 index, CRP and PCT in sepsis group were significantly higher than those in control group [neutrophil CD64 index: 9.03±5.59 vs. 3.18±1.50, CRP (mg/L): 146.9±68.3 vs. 46.5±35.8, PCT (ng/L): 31.82±14.71 vs. 1.87±1.42, all P < 0.05]. ROC curve analysis showed that neutrophil CD64 index, CRP and PCT had certain diagnostic value for sepsis, the area under ROC curve (AUC) were 0.924, 0.915 and 0.879, respectively, the 95% confidence intervals (95% CI) were 0.871-0.978, 0.855-0.975, 0.807-0.951, respectively, P values were 0.016, 0.017 and 0.026, respectively. Among the three indicators, the diagnostic value of neutrophil CD64 index was much higher. When the optimal cut-off value was 4.32, the sensitivity and specificity were 83.6% and 88.7%, respectively, which were higher than the sensitivity (75.1%, 76.3%) and specificity (87.2%, 82.5%) of CRP and PCT. Conclusion:Neutrophil CD64 index is a valuable biomarker for the diagnosis of sepsis in ICU.

There are many problems existing in the basic teaching of traditional surgery, such as much more content, difficult operation, fewer learning hours, more passive acceptance while less active learning and so on. Flipped class based on the WeChat and team-based learning (TBL) is based on the on-line and off-line class. We can use WeChat group and subscription to issue relevant learning materials, learning tasks and test before class. Also, we can summarize and explain incisively by discussion after field operation in class, and answer and test in the way of WeChat discussion after class. Finally, the three-dimensional hybrid teaching will be condensed and sublimated by brand competition based on the basis of surgery, achieving knowledge transfer before class, knowledge internalization in class, knowledge consolida-tion after class and brand competition sublimation, in order to improve the teaching effect of surgical basis.

There is increasing recognition of the importance of the quality of life (QOL) since it became an endpoint of clinical practices, a variety of disease-specific quality of life instruments have been developed and used as a means of assessing clinical interventions. Traditional evaluation was performed by researchers who generally ignore the subjective feeling from pa-tiens. At present, many evaluation criteria has paid more attention to the patient's subjective feelings into the scoring system, the assessment tool of patient-reported outcome (PRO) is usually the patient self-rating scale or questionnaire. As a common complica-tions of terminal stages of cancer, the treatment of bone metastases is usually conservative, improving or maintaining the quality of life of patients has been the consensus. Bone metastases trials have employed QLQ-C30 which raised by Europe Organization for Research and Treatment of Cancer (EORTC) or other generic health related QOL measurement, such as functional assessment of cancer therapy-general (FACT-G) and the MOS 36-item short from health survey (SF-36). But they lack specificity and accuracy in the assessment. EORTC QLQ-BM22 scale is considered as a bone metastases specific scale which was introducted in 2009, after the reliability, validity, cross-cultural adaptability verification, with the combination of EORTC QLQ-C 30 or used alone, has in-creasingly applied to clinical trials and practice for QOL assessment of bone metastatic cancer patients in recent years. It complete the EORTC evaluation system, which has significant value for assessing efficacy. EORTC QLQ-BM 22 has been translated into sim-plified Chinese and evaluated its utility, could be used in China as an effective questionnaire in evaluating the QOL for patients with bone metastases. In this study, current situation and progress of QOL measuring tools for bone metastases patients is re-viewed, in order to help researchers choose appropriate scale and better assess the efficacy, find the pros and cons to guide the clinical treatment decision.

Objective:To investigate the clinical efficacy and effects on hemorheology of acupuncture therapy combined with gaba-pentin in the treatment of patients with tension headache. Methods:Totally 92 cases of patients with tension headache were randomly divided into the observation group (n=46) and the control group (n=46) according to the random number table. The control group was given gabapentin, while the observation group was treated with acupuncture therapy on the basis of treatment in the control group. The treatment course was 4 weeks. The clinical efficacy, changes of the headache indices, VAS score and hemorheology levels before and after the treatments in the two groups were compared, and the incidence of adverse reactions was observed as well. Results:The to-tal effective rate of the observation group (93. 48%) was significantly higher than that of the control group (73. 91%, P<0. 05). Af-ter the treatment, the headache indices in both groups significantly decreased (P<0. 05), and the decrease in the observation group was more significant than that in the control group (P<0. 05). The VAS scores in both groups significantly decreased after the treat-ment (P<0. 05), and the decrease in the observation group was more significant than that in the control group (P<0. 05). The plas-ma viscosity, hematocrit and platelet aggregation rate in both groups significantly decreased after the treatment (P<0. 05), and the decrease in the observation group was more notable than that in the control group (P<0. 05). No severe adverse reactions were shown in both groups during the treatment course. Conclusion: Acupuncture therapy combined with gabapentin in the treatment of patients with tension headache shows striking effects, which can improve hemorheology with promising safety and deserves further studies.

Objective To investigate the clinical efficacy of ginkgo leaf tablets in patients with forgotten-type mild cognitive impairment (aMCI) and its effect on soluble glycosylated terminal product receptor (sRAGE) and soluble low-density lipoprotein receptor-associated protein 1 (sLRP-1).Methods A total of 124 patients with aMCI were divided into observation group (n =62) and control group (n =62),treated by nimodipine tablets (30 mg) three times a day,ginkgo leaf tablets for 3 times a day,respectively.The changes of MoCA score,levels of sRAGE,sLRP-1 and the occurrence of adverse reactions before and after treatment were compared between the two groups.Results The scores of MoCA were improved in both groups after treatment,and the observation group improved more after treatment,and the differences were statistically significant (P ＜ 0.0 5).There was no significant difference in plasma sRAGE and sLRP-1 levels between the two groups (P ＞ 0.05),but the plasma sRAGE increased and the sLRP-1 level decreased after treatment in two groups (P ＜ 0.05).Plasma sRAGE was higher in the treatment group than that in the control group,while the sLRP-1 level was lower than that in the control group (P ＜0.05).Conclusion Ginkgo leaf tablets have a significant clinical effect for aMCI patients,which can increase level of plasma sRAGE and decrease sLRP-1.